Results of hyperamplification of centrosomes in naturally developing tumors of dogs.

Results of hyperamplification of centrosomes in naturally developing tumors of dogs.
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狗自然发育的肿瘤中中心体过度扩增的结果。

DOI:
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发表时间:
2001
影响因子:
1
通讯作者:
H. Tsujimoto
H. Tsujimoto
中科院分区:
农林科学4区
文献类型:
--
作者:
A. Setoguchi;M. Okuda;E. Nishida;M. Yazawa;T. Ishizaka;S. Hong;M. Hisasue;R. Nishimura;N. Sasaki;Y. Yoshikawa;K. Masuda;K. Ohno;H. Tsujimoto

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目的 评价中心体过度扩增在犬自然发生肿瘤中的作用。 样本群体 来自9只患有肿瘤(横纹肌肉瘤、骨肉瘤、软骨肉瘤、粘液肉瘤和乳腺肿瘤)的犬和2只犬骨肉瘤细胞系的肿瘤标本。 程序 使用3种中心体蛋白抗体(即抗γ-微管蛋白、抗BRCA 1和抗中心周蛋白)进行免疫组织化学分析。中心体的双重免疫染色用于确认这些抗体对中心体的特异性。通过聚合酶链反应-单链构象多态性分析对犬p53基因进行突变分析,并通过使用抗MDM 2抗体的免疫组织化学分析评价犬MDM 2蛋白的表达。 结果 免疫组化分析狗骨肉瘤细胞系与明显的非整倍体显示频繁的超扩增的中心体的骨肉瘤细胞系。在9例肿瘤组织中均检测到类似的高扩增中心体。在每个肿瘤组织中具有超扩增中心体的细胞(3至20个/细胞)的频率范围为9.50%至48.1%,而在这些狗的正常淋巴结中未观察到中心体超扩增。9例肿瘤中8例p53基因突变或MDM 2过表达,或两者兼有。 结论和临床相关性 犬的各种类型的自然发生的肿瘤通常具有与染色体不稳定性相关的中心体过度扩增。中心体的过度扩增是一种新的肿瘤标记物,可用于犬临床标本的细胞学和组织学检查。
OBJECTIVE To evaluate results of centrosome hyperamplification in naturally developing tumors of dogs. SAMPLE POPULATION Tumor specimens from 9 dogs with tumors (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, myxosarcoma, and mammary gland tumor) and 2 canine osteosarcoma cell lines. PROCEDURE 3 antibodies for centrosome proteins (ie, anti-gamma-tubulin, anti-BRCA1, and anti-pericentrin) were used for immunohistochemical analysis. Double immunostaining for centrosomes was used to confirm the specificity of these antibodies for centrosomes. Mutational analysis of the canine p53 gene was carried out by polymerase chain reaction-single-strand conformation polymorphism analysis, and expression of canine MDM2 protein was evaluated by use of immunohistochemical analysis, using anti-MDM2 antibody. RESULTS Immunohistochemical analysis of dog osteosarcoma cell lines with apparent aneuploidy revealed frequent hyperamplification of centrosomes in the osteosarcoma cell lines. Similar hyperamplified centrosomes were detected in the tumor tissues from all of the 9 tumors. The frequency of cells with hyperamplified centrosomes (3 to 20/cell) in each tumor tissue ranged from 9.50 to 48.1%, whereas centrosome hyperamplification was not observed in normal lymph nodes from these dogs. In 8 of the 9 tumors, mutation of p53 gene or overexpression of MDM2, or both, was detected. CONCLUSIONS AND CLINICAL RELEVANCE Various types of naturally developing tumors in dogs often have hyperamplification of centrosomes associated with chromosome instability. Hyperamplification of centrosomes is a novel tumor marker for use in cytologic and histologic examinations of clinical specimens obtained from dogs.
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